KR101812418B1 - Novel alkylphosphocholine derivatives and the pharmaceutical composition comprising thereof - Google Patents

Abstract

The present invention relates to a novel alkylphosphocholine derivative compound having anticancer activities, a use thereof to produce drugs for cancer treatment, a pharmaceutical composition containing the same, a treatment method using the composition, and a production method for the same. According to the present invention, novel alkylphosphocholine derivatives are capable of remarkably suppressing growth of cancer cells, thereby being useful for treating, ameliorating, relieving, and preventing cancer.

Description

TECHNICAL FIELD The present invention relates to novel alkylphosphocholine derivatives and pharmaceutical compositions comprising the same,

The present invention relates to a novel compound having anticancer activity, their use in the manufacture of a medicament for the treatment of cancer, a pharmaceutical composition containing them, a therapeutic method using the composition, and a method for producing the same.

Currently, the number of deaths due to cancer and cancer is continuously increasing due to rapid population aging and changes in lifestyle. Among cancer deaths, cancer deaths are the number one cause of death among men and women. Cancer incidence and mortality are increasing every year in Korea as well as globally, and it is necessary to develop a more powerful anticancer drug that can treat cancer.

 Since various anticancer drugs developed before the 1990s targeted DNA or microtubules present in the cells as cytotoxic drugs, they showed therapeutic effects on cancer cells, but they also attack normal cells, resulting in various adverse side effects. Since the 1990s, cancer biologics have been identified and targeted cancer drugs have emerged that can only attack specific cancer cells. These target anticancer drugs are actively studied as drugs that can reduce the adverse effects of existing cytotoxic anticancer drugs because they target the signal transduction pathway, angiogenesis, cell cycle regulator and cell death of cancer cells.

 Studies on alkylphosphocholines (APCs) among several candidate anticancer agents have begun with the synthesis of several metabolically stable derivatives of lysophosphatidylcholine (LPC) in studies related to immunomodulation in the 1960s. It has been found that derivatives synthesized in this process have not only an immunosuppressive action but also excellent anticancer activity. Thereafter, miltefosine, an APC derivative, has been developed as a therapeutic agent for skin metastasis in breast cancer and is currently used in clinical practice.

It has been reported that the action mechanism of APCs such as miltefosine induces apoptosis by inhibiting the PI3K / Akt signaling pathway. [Reference: G.A. Ruiter et al., Anticancer Drugs 14 (2003) 167-173, F. Mollinedo et al., Curr. Med. Chem. 11 (2004) 3163-3184. Akt is highly active in cancer cells with serine / threonine kinase and can be a good point in chemotherapy because it carries various sub-signals related to cell growth, proliferation and death. APCs are structurally similar to phospholipids, which act on cell membrane DNA, and act on the PI3K / Akt signaling pathway around cell walls to inhibit the signal related to the proliferation and survival of cancer cells. Therefore, Is expected to have the advantage of not exhibiting lethal side effects such as mutagenesis of [WJ van Blitterwijk, M. Verheij, Curr. Pharm. Des 14 (2008) 2061-2074.]. However, the use of miltafosin is limited due to its narrow therapeutic index, gastrointestinal toxicity, hemolytic action, and the anticancer efficacy of APCs is relatively weak compared with other chemotherapeutic drugs. Therefore, a new therapeutic agent [I. Ahmed, et al., Cancer Res. 57 (1997) 1915-1921.].

G.A. Ruiter et al., Anticancer Drugs 14 (2003) 167-173, F. Mollinedo et al., Curr. Med. Chem. 11 (2004) 3163-3184 W.J. van Blitterwijk, M. Verheij, Curr. Pharm. Des 14 (2008) 2061-2074. I. Ahmed, et al., Cancer Res. 57 (1997) 1915-1921.

The inventors of the present invention have conducted intensive studies to develop a novel alkylphosphocholine compound having excellent anticancer activity. As a result, they found that the novel alkylphosphocholine derivatives have excellent activity of inhibiting the proliferation of cancer cells and completed the present invention.

It is therefore an object of the present invention to provide novel compounds.

Another object of the present invention is to provide a pharmaceutical composition comprising a novel compound as an active ingredient.

It is another object of the present invention to provide a pharmaceutical composition for preventing and treating cancer comprising the above-mentioned compounds.

It is still another object of the present invention to provide a method for producing the same.

It is a further object of the present invention to provide their use in the manufacture of medicaments for the treatment of cancer.

It is another object of the present invention to provide a method of treating cancer comprising administering a therapeutically effective amount of a pharmaceutical composition comprising the compounds.

According to the above object, the present invention provides a compound represented by the formula (I):

(I)

In the above formula, -OR is substituted at the ortho, meta, or para position of benzene,

_Wherein R is- _C10-30 straight or branched chain alkyl; Or -C _10-30 alkyl comprising 1 to 5 double bonds.

Preferably, R is selected from -C _15-20 straight chain alkyl; -C _15-23 straight chain alkyl containing one double bond; -C _15-20 straight chain alkyl containing two double bonds; And -C _15-20 straight chain alkyl comprising three double bonds.

More preferably, R is -Ci- _17-19 straight chain alkyl; -C _15-23 straight chain alkyl containing one double bond between carbon numbers 8 through 14; -C _17-19 straight chain alkyl comprising two double bonds between carbon number 8 and carbon number 14; And -C _17-19 straight chain alkyl comprising three double bonds between carbon numbers 8 to 18 carbons. The alkyl containing the double bond (alkenyl) includes both (Z) and (E), preferably (Z).

More preferably, R is selected from the group consisting of octadecyl, (Z) -hexadec-9-enyl ((Z) -hexadec-9-enyl) octadec-9-enyl), (Z) -docos-13-enyl ((Z) -docos-13-enyl), (9Z, 12Z) 12Z) -octadeca-9,12-dienyl) and (9Z, 12Z, 15Z) -octadeca-9,12,15-trienyl ((9Z, 12Z, 15Z) -octadeca-9,12,15- ). ≪ / RTI >

The compounds represented by formula (I) of the present invention are as follows:

The structural formula of the compound represented by the formula (I) is as shown in the following Tables 1 to 2.

[Table 1]

[Table 2]

A specific method for preparing the novel compound of formula (I) is shown in Scheme 1.

 [Reaction Scheme 1]

(A) methyl 2- (hydroxyphenyl) acetate (Formula 1) is reacted with a -C _10-30 straight or branched chain alkyl bromide of Formula 2 in the presence of a base, a -C _{10 -30} alkyl bromide, -C _10-30 straight and branched chain alkyl chloride, -C _10-30 alkyl chloride containing 1 to 5 double bonds, to produce a compound of formula 3 ;

(b) reducing the compound of formula (3) under lithium aluminum hydride to produce a compound of formula (4);

(c) reacting a compound of formula (IV) with 2-chloro-2-oxo-1,3,2-dioxaphospholane of formula (5) to produce a compound of formula (6); And

(d) reacting the compound of formula (6) with trimethylamine to produce a compound of formula (I). Wherein R is as hereinbefore defined with respect to formula (I).

In step (a), methyl 2- (hydroxyphenyl) acetate (Formula 1) is reacted with methyl 2- (2-hydroxyphenyl) -hydroxyphenyl) is one selected from the group consisting of acetate, -C _10-30 alkyl, including -C _10-30 straight or branched chain alkyl bromide, 1 to 5 double bond of formula (2) in the presence of a base bromide , -C _10-30 straight and branched chain alkyl chlorides, and -C _10-30 alkyl chlorides containing 1 to 5 double bonds at 50-70 ° C. The reaction may be carried out in the presence of a base, preferably in the presence of potassium carbonate.

In step (b), the compound of formula (4) may be prepared by reducing the compound of formula (3) prepared in step (a) at room temperature under lithium aluminum hydride.

 In step (c), the compound of formula (IV) prepared in step (b) is reacted with 2-chloro-2-oxo-1,3,2-dioxaphospholane of formula (5) .

In step (d), the compound of formula (I) may be reacted with trimethylamine at -70 ° C to 80 ° C.

The present invention provides a pharmaceutical composition comprising the compound of formula (I) as an active ingredient.

(I)

In the above formula, -OR is substituted at the ortho, meta, or para position of benzene,

R is the same as defined above.

Preferably, a pharmaceutical composition for preventing and treating cancer comprising the compound of the formula (I) as an active ingredient is provided.

Examples of the cancer include breast cancer, lung cancer, liver cancer, kidney cancer, colon cancer, rectal cancer, stomach cancer, prostate cancer, bladder cancer, uterine cancer, bone cancer, testicular cancer, ovarian cancer, epidermal cancer, lymph node cancer, soft tissue cancer, head and neck cancer, Thyroid cancer, esophageal cancer, leukemia, neuroblastoma, and the like.

The pharmaceutical composition of the present invention may further contain at least one pharmaceutically acceptable carrier in addition to the compound represented by the above-mentioned formula (I) for administration. The pharmaceutically acceptable carrier may be a mixture of saline, sterilized water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more of these components. If necessary, an antioxidant, , And other conventional additives such as a bacteriostatic agent may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Accordingly, the composition of the present invention may be a patch, a liquid, a pill, a capsule, a granule, a tablet, a suppository, or the like. These formulations may be formulated according to the usual methods used in the art for formulation in accordance with each disease and / or according to the ingredients, or the methods disclosed in Remington's Pharmaceutical Science (recent edition), Mack Publishing Company, Easton PA.

The composition of the present invention may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically) depending on the intended method, and the dose may be appropriately determined depending on the body weight, age, sex, The range varies depending on diet, administration time, method of administration, excretion rate, and severity of the disease. The daily dose of the derivative compound of the formula (1) of the present invention is about 1 to 500 mg / kg, preferably 5 to 100 mg / kg, and can be administered once or several times a day.

The pharmaceutical composition of the present invention may further contain at least one active ingredient which exhibits the same or similar pharmacological effect in addition to the compound represented by the general formula (I).

The present invention provides a method of preventing or treating cancer, comprising administration of a therapeutically effective amount of a compound represented by formula (I).

As used herein, the term "therapeutically effective amount" refers to the amount of the compound of formula (1) effective in the prevention or treatment of cancer.

The method for preventing or treating cancer of the present invention not only treats the disease itself before the manifestation of symptoms, but also inhibits or avoids the symptoms thereof, by administering the compound represented by the above formula (I). In the management of disease, the prophylactic or therapeutic dose of a particular active ingredient will vary depending on the nature and severity of the disease or condition, and the route by which the active ingredient is to be administered. The frequency of dose and dose will vary with the age, weight and response of the individual patient. Appropriate dosing regimens can be readily selected by those of ordinary skill in the art which will of course consider these factors. In addition, the method for preventing or treating cancer of the present invention may further comprise administration of a therapeutically effective amount of a further active agent which is useful for treating a disease together with the compound represented by Formula 1 above, Together with the compound of formula (I), can exhibit synergistic or additive effects.

The present invention also provides a compound represented by the above formula (I) in the manufacture of a medicament for the treatment of cancer. The compound represented by the above formula (I) for the manufacture of a medicament may be mixed with a pharmaceutically acceptable adjuvant, diluent, carrier or the like, and may be synergistically prepared with a combination preparation together with other active agents.

The matters mentioned in the use, composition and treatment method of the present invention are applied equally unless they are mutually contradictory.

The alkylphosphocholine derivatives of formula (I) according to the present invention can greatly inhibit the growth of cancer cells and thus can be usefully used for preventing, alleviating, improving and treating cancer.

Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the examples.

The reagents and solvents mentioned below were purchased from Aldrich-Sigma et al. Unless otherwise noted, and the silica gel for column chromatography was Merck Kiesegel 60 Art 9385 (230-400 mesh). NMR analysis for the structural analysis of the synthesized compounds used a Brucker Avance 400 spectrometer ( ¹ H NMR: 400 MHz; ¹³ C NMR: 100 MHz).

Preparation of novel alkylphosphocholine derivative compounds

The process for preparing the compounds of formula I is illustrated by the following examples.

Example 1: Preparation of 2- (octadecyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-1)

Step 1: Preparation of methyl 2- (2- (octadecyloxy) phenyl) acetate (3a)

(1a, 0.50 g, 3.01 mmol) was dissolved in N, N-dimethylformamide (5 mL), potassium carbonate (1.25 g, 9.03 mmol) was added at room temperature, and 30 Lt; / RTI > Then, 1-bromooctadecane (1.32 g, 3.97 mmol) is added and the temperature is refluxed at 60 占 폚. When the reaction is complete, the reaction mixture is cooled to room temperature, distilled water is added, extracted three times with ethyl acetate, and washed with brine. The organic layer was dried over anhydrous MgSO ₄ and the solvent was removed under reduced pressure. The mixture was then separated by silica gel column chromatography (ethyl acetate / hexane = 1: 20) to give the title compound (0.57 g, 45%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.25-7.20 (m, 1H), 7.19-7.15 (m, 1H), 6.92-6.87 (m, 1H), 6.86-6.82 (m, 1H), 3.95 ( t, J = 6.4 Hz, 2H ), 3.68 (s, 3H), 3.63 (s, 2H), 1.80-1.70 (m, 2H), 1.49-1.38 (m, 2H), 1.38-1.01 (m, 32H) , 0.88 (t, J = 6.8 Hz, 3 H).

Step 2: Preparation of 2- (2- (octadecyloxy) phenyl) ethanol (4a)

To a solution of lithium aluminum hydride (0.11 g, 2.99 mmol) in tetrahydrofuran (10 mL), the compound 3a (0.50 g, 1.19 mmol) prepared in the above step 1 was dissolved in tetrahydrofuran Is slowly added dropwise at 0 < 0 > C and stirred at room temperature for 30 minutes. After the reaction, ethyl acetate and a small amount of water were added and stirred for 10 minutes to remove excess lithium aluminum hydride. The reaction mixture was filtered through Celite to remove lithium aluminum hydride residues and then washed with ethyl acetate. The filtered solution was concentrated under reduced pressure to remove the solvent and then separated by silica gel column chromatography (ethyl acetate / hexane = 1: 9) to give the title compound (0.34 g, 73%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.23-7.13 (m, 2H), 6.93-6.82 (m, 2H), 3.97 (t, J = 6.4 Hz, 2H), 3.84 (q, J = 12.2 Hz (M, 2H), 2.92 (t, J = 6.4 Hz, 2H), 1.85-1.74 (m, 2H), 1.71 (t, J = 5.8 Hz, 1H), 1.51-1.40 m, 32H), 0.88 (t, J = 6.8 Hz, 3H).

Step 3: Preparation of 2- (octadecyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-1)

(0.31 g, 0.79 mmol) and triethylamine (0.34 ml, 2.38 mmol) were added to benzene (5 ml) and the mixture was completely dissolved. (0.24 ml, 2.38 mmol) was added to the solution. After that, the temperature was slowly raised to room temperature and stirred for 5 hours. When the reaction is complete, the precipitated triethylamine hydrochloride is filtered off, washed with benzene and concentrated. It is then dissolved in acetonitrile and transferred to a pressure-resistant container. After cooling to -78 deg. C, trimethylamine (2 ml) was added under nitrogen and sealed, followed by stirring at 65 deg. C for 15 hours. After the reaction was completed, the reaction mixture was cooled to room temperature and the solvent was removed. The residue was purified by silica column chromatography (chloroform / methanol = 9: 1 → chloroform / methanol / water = 6: 2.5: 4) to obtain the title compound (0.24 g, 55% .

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.25-7.14 (m, 2H), 6.95-6.82 (m, 2H), 4.14-4.03 (m, 4H), 4.00 (t, J = 6.4 Hz, 2H) , 3.54-3.48 (m, 2H), 3.19-3.13 (s, 9H), 2.98 (t, J = 6.8 Hz, 2H), 1.86-1.78 (m, 2H), 1.56-1.46 (m, 2H), 1.46 -1.21 (m, 32H), 0.92 (t, J = 6.8 Hz, 3H).

_{^{13 CNMR (100 MHz, CD 3}} OD) δ 158.5, 132.1, 128.9, 127.9, 121.3, 112.4, 69.1, 67.4, 66.4, 60.2, 54.7 (3C), 33.1, 30.8 (13C), 30.5 (2C), 27.3, 23.8, 14.5.

Example 2: Preparation of (Z) -2- (hexadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-2)

Step 1: Preparation of (Z) -Methyl 2- (hexadec-9-enyloxy) phenyl acetate [(Z) -methyl 2- (hexadec-9- enyloxy) phenylacetate]

(Z) -16-bromohexadec-7-ene ((Z) -16 (2-hydroxyphenyl) -bromohexadec-7-ene, 0.38 g) was used to obtain the title compound (0.17 g, 48%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.18 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 5.38-5.32 (m, 2H), 3.93 (t, J 2H), 1.39-1.39 (m, 2H), 1.39-1.30 (m, 2H), 3.68 (s, 3H) 1.21 (m, 16H), 0.88 (t, J = 6.8 Hz, 3H).

Step 2: Preparation of (Z) -2- (2- (hexadec-9-enyloxy) phenyl)

The compound 3b (0.17 g) obtained in the above step 1 was reduced with lithium aluminum hydride (0.11 g) to obtain the title compound (0.13 g, 82%) in the same synthetic method as in step 2 of Example 1 above.

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.23-7.13 (m, 2H), 6.92-6.82 (m, 2H), 5.40-5.30 (m, 2H), 3.97 (t, J = 6.4 Hz, 2H) 2H), 3.84 (q, J = 12.2,2H), 2.92 (t, J = 6.4 Hz, 2H), 2.06-1.97 (m, 4H), 1.84-1.72 , 1.41-1.19 (m, 16H), 0.88 (t, J = 6.8 Hz, 3H).

Step 3: (Z) -2- (hexadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-2)

The compound 4b (0.13 g) obtained in the above step 2 was reacted with 2-chloro-2-oxo-1,3,2-dioxasporeane (0.11 mL) in the same manner as in the step 3 of Example 1, To give the title compound (0.15 g, 79%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.14-7.01 (m, 2H), 6.83-6.68 (m, 2H), 5.30-5.16 (m, 2H), 4.02-3.90 (m, 4H), 3.88 ( t, J = 6.4 Hz, 2H ), 3.42-3.35 (m, 2H), 3.07-3.00 (s, 9H), 2.86 (t, J = 6.4 Hz, 2H), 1.98-1.86 (m, 4H), 1.74 -1.64 (m, 2H), 1.45-1.34 (m, 2H), 1.34-1.12 (m, 16H), 0.80 (t, J = 6.8 Hz, 3H).

^{13 C NMR (100 MHz, CD} 3 OD) δ 158.5, 132.2, 130.9 (2C), (3C) 128.9, 121.3, 112.4, 69.1, 67.3, 66.3, 60.2, 54.7, 33.0, 30.9 (8C), 28.2 (2C ), 27.4, 23.8, 14.6.

Example 3 Synthesis of (Z) -2- (octadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-3)

Step 1: Preparation of (Z) -methyl 2- (octadec-9-enyloxy) phenylacetate (3c)

(0.12 g) and (Z) -16-bromooctadec-9-ene ((Z) -16-bromooctadec-9-ene, 0.25 g) were used in the same synthetic method as in step 1 of Example 1 above To give the title compound (0.19 g, 61%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.25-7.20 (m, 1H), 7.20-7.12 (m, 1H), 6.94-6.87 (m, 1H), 6.87-6.81 (m, 1H), 5.42- 5.28 (m, 2H), 3.95 (t, J = 6.3 Hz, 2H), 3.68 (s, 3H), 3.63 (s, 2H), 2.06-1.96 (m, 4H), 1.80-1.70 (m, 2H) , 1.50-1.39 (m, 2H), 1.39-1.11 (m, 20H), 0.88 (t, J = 6.8 Hz, 3H).

Step 2: Preparation of (Z) -2- (2- (octadec-9-enyloxy) phenyl)

The compound 3c (0.19 g) obtained in the above step 1 was reduced with lithium aluminum hydride (0.04 g) to obtain the title compound (0.14 g, 80%) in the same synthetic method as in step 2 of Example 1 above.

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.22-7.08 (m, 2H), 6.92-6.78 (m, 2H), 5.40-5.28 (m, 2H), 3.97 (t, J = 6.4 Hz, 2H) , 3.87-3.79 (m, 2H), 2.92 (t, J = 6.3 Hz, 2H), 2.05-1.93 (m, 4H), 1.84-1.74 (m, 2H), 1.51-1.40 (m, 2H), 1.40 -1.16 (m, 20H), 0.88 (t, J = 6.8 Hz, 3H).

Step 3: Preparation of (Z) -2- (octadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate

Compound 4c (0.14 g) obtained in the above Step 2 was reacted with 2-chloro-2-oxo-1,3,2-dioxasporeane (0.13 mL) in the same manner as in Step 3 of Example 1, To give the title compound (0.1 g, 45%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.13-7.09 (m, 1H), 7.09-7.02 (m, 1H), 6.81-6.70 (m, 2H), 5.29-5.18 (m, 2H), 4.04- 3.90 (m, 4H), 3.86 (t, J = 6.4 Hz, 2H), 3.42-3.35 (m, 2H), 3.06-3.00 (s, 9H), 2.86 (t, J = 6.4 Hz, 2H), 1.97 2H), 1.33-1.10 (m, 28H), 0.79 (t, J = 6.8 Hz, 3H).

^{13 C NMR (100 MHz, CD} 3 OD) δ 157.1, 130.7, 129.5 (2C), 127.5, 126.5, 120.0, 111.0, 67.7, 66.0, 64.9, 58.7, 53.2 (3C), 31.7, 29.5 (14C), 28.2 (2C), 27.3, 23.8, 14.8.

Example 4: Preparation of (Z) -2- (docos-13-enyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-4)

Step 1: (Z) -methyl 2- (docos-13-enyloxy) phenylacetate (3d)

(0.12 g) and (Z) -16-bromodocos-9-ene ((Z) -16-bromodocos-9-ene, 0.24) were used in the same manner as in step 1 of Example 1, To give the compound (0.13 g, 38%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.25-7.19 (m, 1H), 7.19-7.15 (m, 1H), 6.92-6.86 (m, 1H), 6.86-6.82 (m, 1H), 5.39- 2H), 3.80 (m, 2H), 3.95 (t, J = 6.4 Hz, 2H) , 1.49-1.38 (m, 2H), 1.38-1.16 (m, 28H), 0.88 (t, J = 6.8 Hz, 3H).

Step 2: Preparation of (Z) -2- (2- (docos-13-enyloxy) phenyl)

Compound (3d) (0.13 g) obtained in the above Step 1 was reduced with lithium aluminum hydride (0.02 g) to obtain the title compound (0.08 g, 67%) in the same synthetic method as in Step 2 of Example 1 above.

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.24-7.10 (m, 2H), 6.94-6.81 (m, 2H), 5.43-5.29 (m, 2H), 3.97 (t, J = 6.6 Hz, 2H) , 3.84 (q, J = 12.2 , 2H), 2.92 (t, J = 6.4 Hz, 2H), 2.08-1.96 (m, 4H), 1.85-1.75 (m, 2H), 1.52-1.41 (m, 2H) , 1.41-1.16 (m, 28H), 0.88 (t, J = 6.8 Hz, 3H).

Step 3: Preparation of (Z) -2- (docos-13-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate

Compound 4d (0.16 g) obtained in the above Step 2 was reacted with 2-chloro-2-oxo-1,3,2-dioxasporeane (0.11 mL) in the same synthetic method as in Step 3 of Example 1 above To give the title compound (0.1 g, 49%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.13-7.09 (m, 1H), 7.09-7.02 (m, 1H), 6.81-6.70 (m, 2H), 5.29-5.18 (m, 2H), 4.04- 3.90 (m, 4H), 3.86 (t, J = 6.4 Hz, 2H), 3.42-3.35 (m, 2H), 3.06-3.00 (s, 9H), 2.86 (t, J = 6.4 Hz, 2H), 1.97 2H), 1.33-1.10 (m, 28H), 0.79 (t, J = 6.8 Hz, 3H).

^{13 C NMR (100 MHz, CD} 3 OD) δ 157.1, 130.7, 129.5 (2C), 127.5, 126.5, 120.0, 111.0, 67.7, 66.0, 64.9, 58.7, 53.2 (3C), 31.7, 29.5 (14C), 28.2 (2C), 27.3, 23.8, 14.8.

Example 5 Preparation of 2 - ((9Z, 12Z) -octadeca-9,12-dienyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-5)

Step 1: Preparation of (Z) -methyl 2- (2- ((9Z, 12Z) -octadeca-9,12-dienyloxy) phenylacetate)

(0.2 g) and (6Z, 9Z) -18-bromooctadeca-6,9-diene ((6Z, 9Z) -18-bromooctadeca-6,9 -diene, 0.39 g), the title compound is obtained (0.15 g, 30%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.25-7.20 (m, 1H), 7.20-7.15 (m, 1H), 6.93-6.87 (m, 1H), 6.87-6.82 (m, 1H), 5.43- 5.28 (m, 4H), 3.95 (t, J = 6.4 Hz, 2H), 3.68 (s, 3H), 3.63 (s, 2H), 2.78 (t, J = 6.4 Hz, 2H), 2.10-1.97 (m , 4H), 1.80-1.70 (m, 2H), 1.49-1.40 (m, 2H), 1.40-1.13 (m, 14H), 0.89 (t, J = 6.8 Hz, 3H).

Step 2: Preparation of 2- (2 - ((9Z, 12Z) -octadeca-9,12-dienyloxy)

The compound 3e (0.15 g) obtained in the above step 1 was reduced with lithium aluminum hydride (0.03 g) to obtain the title compound (0.11 g, 78%) in the same synthetic method as in step 2 of Example 1 above.

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.23-7.13 (m, 2H), 6.92-6.82 (m, 2H), 5.43-5.28 (m, 4H), 3.97 (t, J = 6.4 Hz, 2H) , 3.84 (q, J = 12.2, 2H), 2.92 (t, J = 6.4 Hz, 2H), 2.78 (t, J = 6.4 Hz, 2H), 2.09-2.00 (m, 4H), 1.84-1.76 , 2H), 1.51-1.41 (m, 2H), 1.41-1.22 (m, 14H), 0.89 (t, J = 6.8 Hz, 3H).

Step 3: Preparation of 2 - ((9Z, 12Z) -octadeca-9,12-dienyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-

The compound 4e (0.11 g) obtained in the above step 2 was reacted with 2-chloro-2-oxo-1,3,2-dioxaaspolane (0.09 mL) in the same manner as in the step 3 of Example 1 To give the title compound (0.15 g, 94%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.28-7.13 (m, 2H), 6.98-6.82 (m, 2H), 5.50-5.25 (m, 4H), 4.22-4.02 (m, 4H), 4.00 ( t, J = 6.4 Hz, 2H ), 3.56-3.47 (m, 2H), 3.21-3.12 (s, 9H), 2.98 (t, J = 6.4 Hz, 2H), 2.80 (t, J = 6.0 Hz, 2H ), 2.16-1.96 (m, 4H), 1.90-1.74 (m, 2H), 1.59-1.47 (m, 2H), 1.47-1.20 (m, 14H), 0.92 (t, J = 6.8 Hz, 3H).

^{13 C NMR (125 MHz, CD} 3 OD) δ 157.3, 130.9 (2C), 129.8, 127.9 (2C), 127.7, 126.7, 120.1, 111.2, 67.9,66.2, 65.1, 59.0, 53.5 (3C), 31.8, 31.5 , 29.2 (6C), 27.0, 26.2, 26.1, 25.4, 22.5, 13.3.

Example 6 Preparation of 2 - ((9Z, 12Z, 15Z) -octadeca-9,12,15-trienyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate (I-6)

Step 1: Methyl Preparation of 2- (2 - ((9Z, 12Z, 15Z) -octadeca-9,12,15-trienyloxy) phenylacetate (3f)

(3Z, 6Z, 9Z) - 18-bromooctadeca-3,6,9-triene (0.25 g) was obtained in the same manner as in step 1 of Example 1, 18-bromooctadeca-3,6,9-triene, 0.49 g) was used to obtain the title compound (0.18 g, 30%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.25-7.20 (m, 1H), 7.20-7.15 (m, 1H), 6.93-6.87 (m, 1H), 6.87-6.82 (m, 1H), 5.48- 5.27 (m, 6H), 3.95 (t, J = 6.4 Hz, 2H), 3.68 (s, 3H), 3.63 (s, 2H), 2.88-2.64 (m, 4H), 2.13-1.94 (m, 4H) , 1.81-1.69 (m, 2H), 1.49-1.39 (m, 2H), 1.39-1.11 (m, 8H), 1.01-0.93 (m, 3H).

Step 2: Preparation of 2- (2 - ((9Z, 12Z, 15Z) -octadeca-9,12,15-trienyloxy)

The compound 3f (0.17 g) obtained in the above step 1 was reduced with lithium aluminum hydride (0.11 g) to obtain the title compound (0.13 g, 82%) in the same synthetic method as in step 2 of Example 1 above.

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.23-7.14 (m, 2H), 6.92-6.83 (m, 2H), 5.53-5.27 (m, 6H), 3.97 (t, J = 6.4 Hz, 2H) , 3.84 (t, J = 6.4,2H), 2.92 (t, J = 6.4 Hz, 2H), 2.84-2.71 (m, 4H), 2.13-1.94 (m, 4H), 1.84-1.74 , 1.51-1.41 (m, 2H), 1.41-1.23 (m, 8H), 1.00-0.93 (m, 3H).

Step 3: Preparation of 2 - ((9Z, 12Z, 15Z) -octadeca-9,12,15-trienyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate

Compound (4f) (0.09 g) obtained in the above Step 2 was reacted with 2-chloro-2-oxo-1,3,2-dioxaaspolane (0.08 mL) in the same manner as in Step 3 of Example 1 To give the title compound (0.11 g, 84%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.26-7.15 (m, 2H), 6.96-6.82 (m, 2H), 5.51-5.27 (m, 6H), 4.13-4.03 (m, 4H), 4.00 ( t, J = 6.4 Hz, 2H ), 3.54-3.48 (m, 2H), 3.20-3.11 (s, 9H), 2.98 (t, J = 6.4 Hz, 2H), 2.87-2.70 (m, 4H), 2.15 -1.96 (m, 4H), 1.87-1.76 (m, 2H), 1.58-1.46 (m, 2H), 1.46-1.25 (m, 8H), 1.02-0.94 (m, 3H).

^{13 C NMR (125 MHz, CD} 3 OD) δ 157.3, 131.6, 131.0 (2C), 130.0, 128.1, 127.7 (2C), 127.1, 126.7, 120.1, 111.2, 67.9, 66.2, 65.1, 59.0, 53.4 (3C) , 31.8, 29.6 (5C), 27.0, 26.1, 25.4, 25.3, 20.3, 13.5.

Example 7: Preparation of 3- (octadecyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-7)

Step 1: Preparation of methyl 2- (3- (octadecyloxy) phenyl) acetate (3 g)

(1.12 g, 3.97 mmol) using 2- (3-hydroxyphenyl) acetate (1b, 0.5 g) and 1-bromooctadecane (1.32 g, 3.97 mmol) according to the same method as in step 1 of Example 1, g, 89%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.22 (t, J = 7.8 Hz, 1H), 6.86-6.77 (m, 3H), 3.94 (t, J = 6.4 Hz, 2H), 3.69 (s, 3H ), 3.59 (s, 2H), 1.82-1.71 (m, 2H), 1.49-1.39 (m, 2H), 1.39-1.11 (m, 32H), 0.88 (t, J = 6.8 Hz, 3H).

Step 2: Preparation of 2- (3- (octadecyloxy) phenyl) ethanol (4 g)

3 g (0.55 g) of the compound obtained in the above Step 1 was reduced with lithium aluminum hydride (0.12 g) to obtain the title compound (0.39 g, 76%) in the same synthetic method as in Step 2 of Example 1 above.

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.25-7.18 (m, 1H), 6.85-6.74 (m, 3H), 3.94 (t, J = 6.4 Hz, 2H), 3.91-3.82 (m, 2H) , 2.84 (t, J = 6.4 Hz, 2H), 1.84-1.72 (m, 2H), 1.52-1.40 (m, 2H), 1.40-1.19 (m, 32H), 0.88 (t, J = 6.8 Hz, 3H ).

Step 3: Preparation of 3- (octadecyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-7)

4 g (0.32 g) of the compound obtained in the above Step 2 was reacted with 2-chloro-2-oxo-1,3,2-dioxaaspolane (0.25 mL) in the same synthetic method as in Step 3 of Example 1 above To give the title compound (0.36 g, 79%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.19 (t, J = 7.8 Hz, 1H), 6.88-6.83 (m, 2H), 6.79-6.73 (m, 1H), 4.13-4.05 (m, 4H) , 3.96 (t, J = 6.4 Hz, 2H), 3.54-3.49 (m, 2H), 3.19-3.12 (s, 9H), 2.93 (t, J = 6.8 Hz, 2H), 1.82-1.72 (m, 2H ), 1.55-1.44 (m, 2H), 1.44-1.22 (m, 32H), 0.92 (t, J = 6.8 Hz, 3H).

^{13 C NMR (100 MHz, CD} 3 OD) δ 159.3, 140.1, 129.0, 121.0, 115.1, 112.1, 77.9, 72.5, 63.0, 58.8, 53.2 (3C), 36.8, 31.7, 29.4 (13C), 25.9, 22.4, 13.2.

Example  8 : (Z) -3- ( Hexadec -9- Ethyloxy ) Penetil  2-( Trimethylammonio )ethyl Phosphate  (I- 8) of  Produce

Step 1: (Z) -Methyl 2- (3- (hexadec-9-enyloxy) phenyl) acetate (3h)

2- (3-hydroxyphenyl) acetate (1b, 0.14 g) and (Z) -16-bromohexadec-7-ene (0.23 g) were used in the same manner as in step 1 of Example 1, To give the title compound (0.23 g, 71%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.22 (t, J = 7.8 Hz, 1H), 6.88-6.77 (m, 3H), 5.40-5.31 (m, 2H), 3.94 (t, J = 6.6 Hz 2H), 3.69 (s, 3H), 3.59 (s, 2H), 2.08-1.95 (m, 4H), 1.82-1.72 , 16H), 0.88 (t, J = 6.8 Hz, 3H).

Step 2: (Z) -2- (3- (hexadec-9-enyloxy) phenyl) ethanol (4h)

The compound 3h (0.22 g) obtained in the above Step 1 was reduced with lithium aluminum hydride (0.04 g) to obtain the title compound (0.17 g, 84%) in the same manner as in Step 2 of Example 1 above.

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.25-7.18 (m, 1H), 6.82-6.74 (m, 3H), 5.40-5.30 (m, 2H), 3.94 (t, J = 6.4 Hz, 2H) , 3.86 (q, J = 12.2 , 2H), 2.84 (t, J = 6.4 Hz, 2H), 2.06-1.96 (m, 4H), 1.82-1.72 (m, 2H), 1.50-1.42 (m, 2H) , 1.42-1.21 (m, 16H), 0.88 (t, J = 6.8 Hz, 3H).

Step 3: Synthesis of (Z) -3- (hexadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate

Compound 4h (0.17 g) obtained in the above Step 2 was reacted with 2-chloro-2-oxo-1,3,2-dioxasporeane (0.14 mL) in the same manner as in Step 3 of Example 1 to obtain (0.21 g, 86%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.10-7.04 (m, 1H), 6.76-6.70 (m, 2H), 6.67-6.61 (m, 1H), 5.29-5.19 (m, 2H), 4.02- 3.91 (m, 4H), 3.83 (t, J = 6.4 Hz, 2H), 3.42-3.36 (m, 2H), 3.06-3.01 (s, 9H), 2.80 (t, J = 6.8 Hz, 2H), 1.97 2H), 1.32-1.14 (m, 28H), 0.79 (t, J = 6.8 Hz, 3H).

^13C NMR (125 MHz, CD ₃ OD)? 140.4, 129.7, 129.2, 121.2, 115.3 (2C), 112.3 (2C), 67.7, 66.4, 66.2, 59.0, ), 27.0, 26.1, 22.6, 13.4.

Example 9: Preparation of (Z) -3- (octadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-9)

Step 1: (Z) -methyl 2- (3- (octadec-9-enyloxy) phenyl) acetate (3i)

(Z) -1-bromooctadec-9-ene (0.18 g) was used in the same manner as in Step 1 of Example 1, except that 2- (3-hydroxyphenyl) To give the title compound (0.19 g, 66%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.22 (t, J = 7.8 Hz, 1H), 6.86-6.77 (m, 3H), 5.41-5.29 (m, 2H), 3.94 (t, J = 6.6 Hz 2H), 3.69 (s, 3H), 3.59 (s, 2H), 2.07-1.94 (m, 4H), 1.82-1.71 (m, 2H), 1.51-1.40 , 20H), 0.88 (t, J = 6.8 Hz, 3H).

Step 2: (Z) -2- (3- (octadec-9-enyloxy) phenyl) ethanol (4i)

In the same manner as in Step 2 of Example 1, the compound 3i (0.19 g) obtained in the above Step 1 was reduced with lithium aluminum hydride (0.04 g) to obtain the title compound (0.15 g, 85%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.24-7.19 (m, 1H), 6.82-6.74 (m, 3H), 5.40-5.30 (m, 2H), 3.94 (t, J = 6.6 Hz, 2H) 2H), 2.84 (m, 2H), 3.86 (q, J = 12.2,2H), 2.84 (t, J = 6.4 Hz, 2H), 2.06-1.94 (m, 4H), 1.82-1.73 , 1.42-1.12 (m, 20H), 0.88 (t, J = 6.8 Hz, 3H).

Step 3: (Z) -3- (octadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate

The compound 4i (0.15 g) obtained in the above step 2 was reacted with 2-chloro-2-oxo-1,3,2-dioxasporeane (0.13 mL) in the same manner as in the step 3 of Example 1 to obtain To give the compound (0.20 g, 84%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.12-7.01 (m, 1H), 6.78-6.58 (m, 3H), 5.32-5.16 (m, 2H), 4.10-3.90 (m, 4H), 3.84 ( t, J = 6.4 Hz, 2H ), 3.43-3.36 (m, 2H), 3.07-3.01 (s, 9H), 2.80 (t, J = 6.8 Hz, 2H), 1.98-1.86 (m, 4H), 1.70 -1.60 (m, 2H), 1.42-1.32 (m, 2H), 1.32-1.12 (m, 20H), 0.79 (t, J = 6.8 Hz, 3H).

^{13 C NMR (100 MHz, CD} 3 OD) δ 159.3, 140.1, 129.5, 129.4, 129.0, 121.0, 115.1, 112.1, 67.5, 66.2, 66.0, 58.8, 53.2 (3C), 36.8, 32.2, 29.3 (9C), 28.8 (2C), 25.9, 22.4, 13.1.

Example 10: Preparation of (Z) -3- (docos-13-enyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-10)

Step 1: (Z) -Methyl 2- (3- (docos-13-enyloxy) phenyl) acetate (3j)

Using the same synthetic method as in step 1 of Example 1 above, 2- (3-hydroxyphenyl) acetate (1b, 0.12 g) and Z) -22-bromodocos-9-ene (0.24 g) (0.17 g, 49%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.22 (t, J = 7.8 Hz, 1H), 6.90-6.76 (m, 3H), 5.40-5.30 (m, 2H), 3.94 (t, J = 6.6 Hz 2H), 3.69 (s, 3H), 3.59 (s, 2H), 2.08-1.94 (m, 4H), 1.82-1.71 , 28H), 0.88 (t, J = 6.8 Hz, 3H).

Step 2: (Z) -2- (3- (docos-13-enyloxy) phenyl) ethanol (4j)

The compound 3j (0.17 g) obtained in the above Step 1 was reduced with lithium aluminum hydride (0.03 g) to obtain the title compound (0.12 g, 80%) in the same synthetic method as in Step 2 of Example 1 above.

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.25-7.18 (m, 1H), 6.85-6.74 (m, 3H), 5.40-5.30 (m, 2H), 3.94 (t, J = 6.8 Hz, 2H) 2H), 3.40-3.82 (m, 2H), 2.84 (t, J = 6.4 Hz, 2H), 2.06-1.96 (m, 4H), 1.82-1.72 -1.21 (m, 28H), 0.88 (t, J = 6.8 Hz, 3H).

Step 3: Synthesis of (Z) -3- (docos-13-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate

The compound 4j (0.12 g) obtained in the above step 2 was reacted with 2-chloro-2-oxo-1,3,2-dioxasporeane (0.09 mL) in the same manner as in the step 3 of Example 1, To give the compound (0.09 g, 52%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.11-7.02 (m, 1H), 6.78-6.59 (m, 3H), 5.30-5.16 (m, 2H), 4.04-3.90 (m, 4H), 3.84 ( t, J = 6.4 Hz, 2H ), 3.43-3.35 (m, 2H), 3.09-2.98 (s, 9H), 2.80 (t, J = 6.8 Hz, 2H), 1.98-1.86 (m, 4H), 1.70 -1.59 (m, 2H), 1.42-1.32 (m, 2H), 1.32-1.10 (m, 28H), 0.80 (t, J = 6.8 Hz, 3H).

^{13 C NMR (100 MHz, CD} 3 OD) δ 160.7, 141.5, 130.9 (2C), 130.4, 122.4, 116.5, 113.5, 68.9, 67.6, 67.4, 60.2, 54.7 (3C), 38.3, 33.2, 30.9 (14C) , 28.2, 27.3, 23.8, 14.6.

Example 11: Preparation of 3 - ((9Z, 12Z) -octadeca-9,12-dienyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-11)

Step 1: Methyl 2- (3 - ((9Z, 12Z) -octadeca-9,12-dionyloxy) phenyl) acetate (3k)

(3-hydroxyphenyl) acetate (1b, 0.2 g) and (6Z, 9Z) -18-bromooctadec-6,9-diene (0.39 g) to give the title compound (0.2 g, 40%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.22 (t, J = 7.8 1H), 6.87-6.77 (m, 3H), 5.44-5.28 (m, 4H), 3.94 (t, J = 6.4 Hz, 2H ), 3.69 (s, 3H) , 3.59 (s, 2H), 2.78 (t, J = 6.4 Hz, 2H), 2.11-1.99 (m, 4H), 1.81-1.72 (m, 2H), 1.51-1.40 ( m, 2H), 1.40-1.20 (m, 14H), 0.89 (t, J = 6.8 Hz, 3H).

Step 2: 2- (3 - ((9Z, 12Z) -octadeca-9,12-dienyloxy) phenyl)

The compound 3k (0.18 g) obtained in the above step 1 was reduced with lithium aluminum hydride (0.03 g) to obtain the title compound (0.10 g, 58%) in the same synthetic method as in step 2 of Example 1 above.

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.25-7.18 (m, 1H), 6.83-6.74 (m, 2H), 5.43-5.29 (m, 4H), 3.94 (t, J = 6.6 Hz, 2H) , 3.90-3.82 (m, 2H), 2.94 (t, J = 6.4 Hz, 2H), 2.78 (t, J = 6.4 Hz, 2H), 2.10-2.00 (m, 4H), 1.82-1.73 ), 1.51-1.42 (m, 2H), 1.42-1.18 (m, 14H), 0.89 (t, J = 6.8 Hz, 3H).

Step 3: 3 - ((9Z, 12Z) -octadeca-9,12-dienyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate

The compound 4k (0.10 g) obtained in the above Step 2 was reacted with 2-chloro-2-oxo-1,3,2-dioxaaspolane (0.08 mL) in the same manner as in Step 3 of Example 1 to obtain To give the compound (0.10 g, 71%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.23-7.16 (m, 1H), 7.89-7.82 (m, 2H), 6.80-6.73 (m, 2H), 5.44-5.29 (m, 4H), 4.16- 4.02 (m, 4H), 3.97 (t, J = 6.4 Hz, 2H), 3.54-3.48 (m, 2H), 3.20-3.12 (s, 9H), 2.93 (t, J = 6.8 Hz, 2H), 2.80 (t, J = 6.0 Hz, 2H), 2.14-2.02 (m, 4H), 1.82-1.73 (m, 2H), 1.54-1.45 (m, 2H), 1.45-1.25 (m, 14H), 0.92 (t , ≪ / RTI > J = 6.8 Hz, 3H).

^{13 C NMR (125 MHz, CD} 3 OD) δ 159.5, 140.4, 129.8 (2C), 129.2, 127.9 (2C), 121.3, 115.3, 112.3, 67.7, 66.4, 66.2, 59.0, 53.4 (3C), 37.0,31.5 , 29.3 (6C), 27.0 (2C), 26.1, 25.4, 22.5, 13.3.

Example 12: Preparation of 3 - ((9Z, 12Z, 15Z) -octadeca-9,12,15-trienyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-12)

Step 1: Methyl 2- (3 - ((9Z, 12Z, 15Z) -octadeca-9,12,15-trienyloxy) phenyl)

(3Z, 6Z, 9Z) -18-bromooctadeca-3,6,9-dihydroxyphenyl) acetate (1b, 0.25 g) was obtained in a similar manner as in Step 1 of Example 1, Triene (0.49 g) was used to obtain the title compound (0.23 g, 37%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.22 (t, J = 7.8 Hz, 1H), 6.88-6.78 (m, 3H), 5.54-5.27 (m, 6H), 3.94 (t, J = 6.3 Hz 2H), 3.69 (s, 3H), 3.59 (s, 2H), 2.86-2.66 (m, 4H), 2.13-1.95 (m, 4H), 1.85-1.72 , 2H), 1.40-1.21 (m, 8H), 1.03-0.93 (m, 3H).

Step 2: 2- (3 - ((9Z, 12Z, 15Z) -octadeca-9,12,15-trienyloxy) phenyl)

In the same manner as in Example 8, 3l (0.23 g) of the compound obtained in the above Step 1 was reduced with lithium aluminum hydride (0.04 g) to obtain the title compound (0.12 g, 58%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.25-7.19 (m, 1H), 6.83-6.74 (m, 2H), 5.50-5.27 (m, 6H), 3.94 (t, J = 6.4 Hz, 2H) 2H), 1.41-1.41 (m, 2H), 3.86 (t, J = 6.4, 2H), 2.87-2.71 (m, 6H), 2.13-1.95 1.25 (m, 8H), 1.01-0.93 (m, 3H).

Step 3: 3 - ((9Z, 12Z, 15Z) -octadeca-9,12,15-trienyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate

(0.12 g) was reacted with 2-chloro-2-oxo-1,3,2-dioxasporeane (0.10 mL) to obtain the title compound (0.15 g, 91%).

¹ H NMR (400 MHz, CD ₃ OD)? 7.19 (t, J = 7.8 Hz, 1H), 6.88-6.82 (m, 2H), 6.79-6.73 , 4.13-4.01 (m, 4H), 3.97 (t, J = 6.4 Hz, 2H), 3.53-3.46 (m, 2H), 3.20-3.09 (s, 9H), 2.92 (t, J = 6.8 Hz, 2H ), 2.87-2.71 (m, 4H), 2.18-1.96 (m, 4H), 1.82-1.70 (m, 2H), 1.55-1.44 (m, 2H), 1.44-1.27 (m, 3 H).

^{13 C NMR (125 MHz, CD} 3 OD) δ 159.5, 140.4, 131.6, 130.0, 129.2 (2C), 128.0, 127.7, 127.1, 121.3, 115.4, 112.3, 67.7, 66.4, 66.2, 59.0, 53.4 (3C), 37.0, 29.4 (5C), 27.0, 26.1, 25.4, 25.3, 20.4, 13.6.

Example 13: Preparation of 4- (octadecyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-13)

Step 1: Methyl 2- (4- (octadecyloxy) phenyl) acetate (3m)

The title compound (0.79 g, 62%) was prepared using 2- (4-hydroxyphenyl) acetate (1c, 0.5 g) and 1- bromooctadecane (1.32 g) according to the same method as in step 1 of Example 1, %).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.17 (d, J = 8.8 Hz, 2H), 6.84 (d, J = 8.8 Hz, 2H), 3.93 (t, J = 6.6, 2H), 3.68 (s J = 6.8 Hz, 3H), 3.56 (s, 2H), 1.82-1.70 (m, 2H), 1.48-1.38 (m, 2H), 1.38-1.11 (m, 32H), 0.88 (t,

Step 2: 2- (4- (octadecyloxy) phenyl) ethanol (4m)

The compound 3m (0.18 g) obtained in the above step 1 was reduced with lithium aluminum hydride (0.04 g) to obtain the title compound (0.14 g, 81%) in the same synthetic method as in step 2 of Example 1 above.

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.11 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 8.8 Hz, 2H), 4.23 (t, J = 7.3 Hz, 2H), 3.93 ( (t, J = 6.6 Hz, 2H), 2.86 (t, J = 7.3 Hz, 2H), 1.82-1.71 (m, 2H), 1.51-1.39 (m, 2H), 1.39-1.14 (t, J = 6.8 Hz, 3 H).

Step 3: 4- (Octadecyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate

4m (0.14 g) of the compound obtained in the above Step 2 was reacted with 2-chloro-2-oxo-1,3,2-dioxaaspolane (0.11 mL) in the same manner as in Step 3 of Example 1 to obtain To give the compound (0.04 g, 19%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.07 (d, J = 8.4 Hz, 2H), 6.73 (d, J = 8.8 Hz, 2H), 4.02-3.88 (m, 4H), 3.83 (t, J = 6.4 Hz, 2H), 3.42-3.38 (m, 2H), 3.09-3.00 (s, 9H), 2.77 (t, J = 6.8 Hz, 2H), 1.69-1.59 (m, 2H), 1.41-1.31 ( m, 2H), 1.31-1.11 (m, 32H), 0.80 (t, J = 6.8 Hz, 3H).

^{13 C NMR (100 MHz, CD} 3 OD) δ 159.2, 131.8, 131.1 (2C), 115.5 (2C), 73.9, 69.1, 64.5, 60.2, 54.6 (3C), 37.3, 33.1, 30.8 (13C), 27.2, 23.8, 14.5.

Example 14: Preparation of (Z) -4- (hexadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-14)

Step 1: (Z) -methyl 2- (4- (hexadec-9-enyloxy) phenyl) acetate (3n)

2- (4-hydroxyphenyl) acetate (1c, 0.14 g) and (Z) -16-bromohexadec-7-ene (0.23 g) were used in the same manner as in step 1 of Example 1, To give the title compound (0.27 g, 82%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.18 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 5.38-5.32 (m, 2H), 3.93 (t, J 2H), 1.39-1.39 (m, 2H), 1.39-1.30 (m, 2H), 3.68 (s, 3H) 1.21 (m, 16H), 0.88 (t, J = 6.8 Hz, 3H).

Step 2: (Z) -2- (4- (hexadec-9-enyloxy) phenyl) ethanol (4n)

The compound 3n (0.24 g) obtained in the above step 1 was reduced with lithium aluminum hydride (0.05 g) to obtain the title compound (0.20 g, 88%) in the same synthetic method as in step 2 of Example 1 above.

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.13 (d, J = 8.3 Hz, 2H), 6.85 (d, J = 8.3 Hz, 2H), 5.40-5.30 (m, 2H), 3.93 (t, J = 6.4 Hz, 2H), 3.82 (q, J = 12.2, 2H), 2.81 (t, J = 6.4 Hz, 2H), 2.06-1.96 (m, 4H), 1.81-1.72 (m, 2H), 1.49- 1.40 (m, 2H), 1.40-1.21 (m, 16H), 0.88 (t, J = 6.8 Hz, 3H).

Step 3: (Z) -4- (hexadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate

The compound 4n (0.18 g) obtained in the above Step 2 was reacted with 2-chloro-2-oxo-1,3,2-dioxasporeane (0.15 mL) in the same manner as in Step 3 of Example 1 to obtain (0.21 g, 79%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.06 (d, J = 8.8 Hz, 2H), 6.72 (d, J = 8.8 Hz, 2H), 5.30-5.18 (m, 2H), 4.05-3.88 (m , 4H), 3.80 (t, J = 6.4 Hz, 2H), 3.46-3.38 (m, 2H), 3.10-3.00 (s, 9H), 2.76 (t, J = 6.8 Hz, 2H), 1.98-1.87 ( m, 4H), 1.68-1.58 (m, 2H), 1.41-1.31 (m, 2H), 1.31-1.11 (m, 16H), 0.79 (t, J = 6.8 Hz, 3H).

¹³ C (100 MHz, CD ₃ OD)? 159.2, 131.8, 131.2 (2C), 130.9 (2C), 115.5 (2C), 69.0, 67.8, 67.4, 60.2, 54.7 8C), 28.2, 27.3, 23.8, 14.6.

Example 15: Preparation of (Z) -4- (octadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-15)

Step 1: (Z) -Methyl 2- (4- (octadec-9-enyloxy) phenyl) acetate (3o)

Using 0.2 g of 2- (4-hydroxyphenyl) acetate (1c, 0.15 g) and (Z) -1-bromooctadec-9-ene in the same synthetic method as in step 1 of Example 1 above To give the title compound (0.19 g, 50%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.18 (d, J = 8.7 Hz, 2H), 7.84 (d, J = 8.7 Hz, 2H), 5.40-5.30 (m, 2H), 3.93 (t, J 2H), 1.39-1.39 (m, 2H), 1.39-1. 36 (m, 2H) 1.18 (m, 20H), 0.88 (t, J = 6.8 Hz, 3H).

Step 2: (Z) -2- (4- (octadec-9-enyloxy) phenyl) ethanol (4o)

The compound 3o (0.19 g) obtained in the above step 1 was reduced with lithium aluminum hydride (0.04 g) to obtain the title compound (0.16 g, 89%) in the same synthetic method as in step 2 of Example 1 above.

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.13 (d, J = 8.7 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 5.40-5.30 (m, 2H), 3.93 (t, J = 6.6 Hz, 2H), 3.82 (q, J = 12.2, 2H), 2.81 (t, J = 6.4 Hz, 2H), 2.06-1.95 (m, 4H), 1.81-1.72 (m, 2H), 1.49- 1.39 (m, 2H), 1.39-1.19 (m, 20H), 0.88 (t, J = 6.8 Hz, 3H).

Step 3: (Z) -4- (Octadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate

Compound 4o (0.15 g, 0.44 mmol) obtained in the above Step 2 was dissolved in a mixture of 2-chloro-2-oxo-1,3,2-dioxasporeane (0.14 mL) and To give the title compound (0.15 g, 61%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.06 (d, J = 8.8 Hz, 2H), 6.72 (d, J = 8.8 Hz, 2H), 5.30-5.18 (m, 2H), 4.04-3.88 (m , 4H), 3.81 (t, J = 6.4 Hz, 2H), 3.45-3.36 (m, 2H), 3.09-2.99 (s, 9H), 2.76 (t, J = 6.8 Hz, 2H), 1.98-1.85 ( m, 4H), 1.68-1.58 (m, 2H), 1.41-1.31 (m, 2H), 1.31-1.12 (m, 20H), 0.79 (t, J = 6.8 Hz, 3H).

^{13 C NMR (100 MHz, CD} 3 OD) δ 159.2, 131.8, 131.6, 131.2, 130.9 (2C), 115.5 (2C), 69.1, 67.8, 67.4, 60.2, 54.7 (3C), 37.4, 33.7, 30.7 (9C ), 28.2 (2C), 27.3, 23.8, 14.6.

Example 16: Preparation of (Z) -4- (docos-13-enyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-16)

Step 1: (Z) -Methyl 2- (4- (docos-13-enyloxy) phenyl) acetate (3p)

Using the same synthetic method as in step 1 of Example 1 above, 2- (4-hydroxyphenyl) acetate (1c, 0.12 g) and (Z) -22-bromodocos- To give the compound (0.16 g, 47%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.18 (d, J = 8.7 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 5.40-5.30 (m, 2H), 3.93 (t, J 2H), 1.50-1.39 (m, 2H), 1.39-1.40 (m, 2H) 1.16 (m, 28H), 0.88 (t, J = 6.8 Hz, 3H).

Step 2: (Z) -2- (4- (docos-13-enyloxy) phenyl) ethanol (4p)

The compound 3p (0.16 g) obtained in the above step 1 was reduced with lithium aluminum hydride (0.03 g) to obtain the title compound (0.12 g, 78%) in the same synthetic method as in step 2 of Example 1 above.

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.13 (d, J = 8.3 Hz, 2H), 6.85 (d, J = 8.3 Hz, 2H), 5.40-5.30 (m, 2H), 3.93 (t, J = 6.8 Hz, 2H), 3.82 (q, J = 12.2, 2H), 2.81 (t, J = 6.4 Hz, 2H), 2.10-1.95 (m, 4H), 1.84-1.70 (m, 2H), 1.50- 1.39 (m, 2H), 1.39-1.18 (m, 28H), 0.88 (t, J = 6.8 Hz, 3H).

Step 3: Synthesis of (Z) -4- (docos-13-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate

Compound 4p (0.12 g) obtained in the above Step 2 was reacted with 2-chloro-2-oxo-1,3,2-dioxasporeane (0.08 mL) in the same manner as in Step 3 of Example 1 to obtain To give the compound (0.13 g, 79%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.18 (d, J = 8.8 Hz, 2H), 6.84 (d, J = 8.8 Hz, 2H), 5.41-5.31 (m, 2H), 4.15-4.00 (m , 4H), 3.93 (t, J = 6.4 Hz, 2H), 3.56-3.50 (m, 2H), 3.20-3.12 (s, 9H), 2.89 (t, J = 6.8 Hz, 2H), 2.09-2.00 ( m, 4H), 1.80-1.72 (m, 2H), 1.52-1.43 (m, 2H), 1.43-1.26 (m, 28H), 0.92 (t, J = 6.8 Hz, 3H).

^{13 C NMR (100 MHz, CD} 3 OD) δ 157.8, 130.3, 129.8 (2C), 129.5 (2C), 114.1 (2C), 67.6, 66.4, 66.0, 58.8, 53.3 (3C), 36.0, 31.8, 29.5 ( 14C), 28.2, 27.3, 23.8, 14.6.

Example 17: Preparation of 4 - ((9Z, 12Z) -octadeca-9,12-dienyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-17)

Step 1: Methyl 2- (4- ((9Z, 12Z) -octadeca-9,12-dienyloxy) phenyl) acetate (3q)

In the same manner as in Step 1 of Example 1, 2- (4-hydroxyphenyl) acetate (1c, 0.2 g) and (6Z, 9Z) -18- bromooctadec-6,9- g), the title compound (0.14 g, 29%) is obtained.

^{1 H NMR (400 MHz, CD} 3 OD) δ 8.02-7.96 (m, 1H), 7.20-7.14 (m, 1H), 6.98-6.92 (m, 1H), 6.87-6.81 (m, 1H), 5.43- 5.28 (m, 4H), 4.04 (t, J = 6.6 Hz, 2H), 3.98-3.90 (m, 3H), 3.70-3.53 (m, 2H), 2.78 (t, J = 6.4 Hz, 2H), 2.10 2H), 1.41-1.19 (m, 14H), 0.89 (t, J = 6.8 Hz, 3H).

Step 2: 2- (4 - ((9Z, 12Z) -octadeca-9,12-dienyloxy) phenyl) ethanol (4q)

The compound 3q (0.14 g) obtained in the above step 1 was reduced with lithium aluminum hydride (0.03 g) to obtain the title compound (0.06 g, 42%) in the same synthetic method as in step 2 of Example 1 above.

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.13 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.3 Hz, 2H), 5.44-5.28 (m, 4H), 3.93 (t, J = 6.4 Hz, 2H), 3.82 (q, J = 12.2, 2H), 2.84-2.70 (m, 4H), 2.11-1.96 (m, 4H), 1.82-1.72 (m, 2H), 1.50-1.40 (m , 2H), 1.40-1.22 (m, 14H), 0.89 (t, J = 6.8 Hz, 3H).

Step 3: 4 - ((9Z, 12Z) -octadeca-9,12-dienyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate

The compound 4q (0.06 g) obtained in the above Step 2 was reacted with 2-chloro-2-oxo-1,3,2-dioxasporeane (0.05 mL) in the same manner as in Step 3 of Example 1 to obtain To give the compound (0.08 g, 90%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.19 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 5.43-5.30 (m, 4H), 4.13-4.01 (m , 4H), 3.95 (t, J = 6.4 Hz, 2H), 3.55-3.49 (m, 2H), 3.20-3.13 (s, 9H), 2.89 (t, J = 6.8 Hz, 2H), 2.80 (t, J = 6.0 Hz, 2H), 2.13-2.02 (m, 4H), 1.81-1.72 (m, 2H), 1.54-1.45 (m, 2H), 1.45-1.13 (m, 14H), 0.92 (t, J = 6.8 Hz, 3H).

^{13 C NMR (125 MHz, CD} 3 OD) δ 158.0, 130.6, 130.0 (2C), 129.8 (2C), 128.0 (2C), 114.3 (2C), 67.8, 66.6, 64.7, 59.0, 53.4 (3C), 36.1 , 31.5, 29.3 (6C), 27.0 (2C), 26.1, 25.4, 22.5, 3.3.

Example 18: Preparation of 4 - ((9Z, 12Z, 15Z) -octadeca-9,12,15-trienyloxy) phenethyl 2- (trimethylammonio) ethylphosphate (I-18)

Step 1: Methyl 2- (4 - ((9Z, 12Z, 15Z) -octadeca-9,12,15-trienyloxy) phenyl)

(4-hydroxyphenyl) acetate (1c, 0.25 g) and (3Z, 6Z, 9Z) -18-bromooctadeca-3,6,9- Triene (0.49 g) was used to obtain the title compound (0.26 g, 43%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.18 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 5.54-5.27 (m, 6H), 3.93 (t, J (M, 2H), 1.50-7.24 (m, 2H), 3.68 (s, 3H) 1.40 (m, 2H), 1.40-1.23 (m, 8H), 1.01-0.93 (m, 3H).

Step 2: 2- (4 - ((9Z, 12Z, 15Z) -octadeca-9,12,15-trienyloxy) phenyl)

The compound 3r (0.26 g) obtained in the above step 1 was reduced with lithium aluminum hydride (0.05 g) to obtain the title compound (0.18 g, 75%) in the same synthetic method as in step 2 of Example 1 above.

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.13 (d, J = 8.3 Hz, 2H), 6.85 (d, J = 8.3 Hz, 2H), 5.53-5.27 (m, 6H), 3.93 (t, J (M, 2H), 1.50-1.40 (m, 2H), 3.82 (t, J = 6.4,2H), 2.85-2.71 , 2H), 1.40-1.22 (m, 8H), 1.01-0.93 (m, 3H).

Step 3: 4 - ((9Z, 12Z, 15Z) -octadeca-9,12,15-trienyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate

The compound 4r (0.17 g) obtained in the above step 2 was reacted with 2-chloro-2-oxo-1,3,2-dioxasporeane (0.14 mL) in the same manner as in the step 3 of Example 1 to obtain To give the compound (0.22 g, 90%).

^{1 H NMR (400 MHz, CD} 3 OD) δ 7.19 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 5.46-5.27 (m, 4H), 4.13-4.01 (m , 4H), 3.95 (t, J = 6.4 Hz, 2H), 3.55-3.48 (m, 2H), 3.20-3.11 (s, 9H), 2.89 (t, J = 6.8 Hz, 2H), 2.86-2.70 ( m, 4H), 2.15-1.97 (m, 4H), 1.82-1.70 (m, 2H), 1.55-1.44 (m, 2H), 1.44-1.28 (m, 8H), 1.02-0.92 (m, 3H).

^{13 C NMR (125 MHz, CD} 3 OD) δ 158.1, 131.6, 130.6, 130.0, 129.9 (2C), 128.1, 128.0, 127.7, 127.1, 114.3 (2C), 67.9, 66.6, 66.2, 59.0, 53.4 (3C) , 36.1, 29.3 (5C), 27.0, 26.1, 25.4, 25.3, 20.4, 13.6.

Example 19: Measurement of cytotoxicity against cancer cells

The cancer cell proliferation inhibitory activity of the alkylphosphocholine derivatives prepared in Examples 1 to 18 was measured using MTT assay. Human lung cancer cell A549, liver cancer cell HepG2, breast cancer cell MCF-7, and skin cancer cell A431 were purchased from Korean Cell Line Bank (KCLB) and used for the experiment. All cell lines were cultured in DMEM (Gibco BRL) containing 10% heat-inactivated Fetal Bovine Serum (FBS) as a culture medium in a humidified atmosphere of 37 ° C, 5% CO ₂ in medium, Lt; / RTI > Cells were seeded at 5 × 10 ³ cells per well in a 96-well plate and cultured for 48 hours in a CO ₂ incubator (5% CO ₂ , 37 ° C.) to control the time of exposure of the cells to the drug. 15 μL of Dye Solution (CellTiter96, Promega, Madison, Wis.) Was added to each well and incubated in a CO ₂ incubator (humidified 5% CO ₂ , 37 ^° C) for 4 hours. After incubation, 100 μL of solubilization Solution / Stop Mix (CellTiter96, Promega, Madison, WI) was added to each well and the plate was placed in a sealed container overnight at room temperature in order to completely dissolve the formazan crystals. The optical density was expressed as% inhibition or IC ₅₀ value by measuring the absorbance at 570 nm wavelength using a microplate reader (VersaMax, Molecular Devices, Sunnyvale, CA, USA).

[Table 3] Cytotoxicity of cancer cells

As can be seen in Table 3, the alkylphosphocholine derivatives according to the present invention were found to inhibit the secretion of the known compound,% inhibition at 100 μM, 36.6% in A549 (lung cancer cell line), 31.28% in HepG2 (liver cancer cell line) , 69.44% in MCF-7 (breast cancer cell line), and 35.39% in A431 (skin cancer cell line).

Particularly, as can be seen from the group treated with the compounds I-1, I-7 and I-13, derivatives substituted with an octadecyl group, which is a saturated hydrocarbon, can be obtained from cancer cells A549, HepG2, MCF -7 and A-431 at concentrations of 10 and 100 [mu] M, respectively, compared with the control substance, miltafosin. Furthermore, I-13 showed better cytotoxicity against A549 and HepG2 than miltesin (an inhibition of 90% or more at a concentration of 100 μM) when the octadecyl group was substituted at the para-position.

Further, derivatives in which two double bonds (I-5, I-11, I-17) or three substituted alkyl groups (I-6, I-12 and I-18) are substituted, And showed cytotoxicity superior to or comparable to that of the substance.

On the other hand, in the case of a derivative in which an unsaturated alkyl group having one double bond was substituted, a difference in cytotoxicity was observed depending on the length of the alkyl group. The derivative I-2 in which the hexadec-9-enyloxy group (R = hexadec-9-enyl) was substituted in the ortho-position showed similar cytotoxicity to the control substance or stronger cytotoxicity against all the cell lines retrieved, The derivatives I-8 and I-14 in which the hexadec-9-enyloxy group was substituted at the meta- and para-positions showed much stronger cytotoxicity than the control substance.

As is apparent from the above, the compounds of the present invention show a stronger inhibitory effect on cancer cell proliferation than most of the cell lines searched for compared with the reference substance, miltofosin.

Claims (9)

A compound represented by the formula (I)
(I)

In the above formula, -OR is substituted at the ortho, meta, or para position of benzene,
(Z) -oxadec-9-enyl, (Z) -docos-13-enyl, (9Z, 12Z) -octadeca-9, (9Z, 12Z, 15Z) -octadeca-9,12,15-trienyi. ≪ / RTI > delete delete delete The compound represented by the formula (I) according to claim 1, wherein the compound represented by the formula (I) is any one selected from the group consisting of
2- (octadecyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -2- (hexadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -2- (octadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -2- (docos-13-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
2 - ((9Z, 12Z) -octadeca-9,12-dienyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
2 - ((9Z, 12Z, 15Z) -octadeca-9,12,15-trienyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
3- (octadecyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -3- (hexadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -3- (octadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -3- (docos-13-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
3 - ((9Z, 12Z) -octadeca-9,12-dienyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
3 - ((9Z, 12Z, 15Z) -octadeca-9,12,15-trienyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
4- (octadecyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -4- (hexadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -4- (octadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -4- (docos-13-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
4 - ((9Z, 12Z) -octadeca-9,12-dienyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate and
4 - ((9Z, 12Z, 15Z) -octadeca-9,12,15-trienyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate. 6. The compound according to claim 5, wherein the compound represented by Formula (I) is 2- (octadecyloxy) phenethyl 2- (trimethylammonio) ethylphosphate,
(Z) -2- (hexadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -2- (octadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -2- (docos-13-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
3- (octadecyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -3- (hexadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -3- (octadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -3- (docos-13-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
4- (octadecyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -4- (hexadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -4- (octadec-9-enyloxy) phenethyl 2- (trimethylammonio) ethyl phosphate,
(Z) -4- (docos-13-enyloxy) phenethyl 2- (trimethylammonio) ethylphosphate. 6. A pharmaceutical composition for preventing or treating cancer, comprising the compound according to any one of claims 1, 5, and 6 as an active ingredient. The method of claim 7, wherein the cancer is selected from the group consisting of breast cancer, lung cancer, liver cancer, kidney cancer, colon cancer, rectal cancer, stomach cancer, prostate cancer, bladder cancer, uterine cancer, metastatic cancer, bone cancer, testicular cancer, ovarian cancer, , Head and neck cancer, thyroid cancer, esophageal cancer, leukemia, and neuroblastoma.

(a) reacting methyl 2- (hydroxyphenyl) acetate (Formula 1) with -C _10-30 straight or branched chain alkyl bromide of Formula 2 in the presence of a base, -C _10-30 alkyl Bromide, -C _10-30 straight and branched chain alkyl chlorides, -C _10-30 alkyl chlorides containing 1 to 5 double bonds to produce a compound of formula 3;
(b) reducing the compound of formula (3) under lithium aluminum hydride to produce a compound of formula (4);
(c) reacting a compound of formula (IV) with 2-chloro-2-oxo-1,3,2-dioxaphospholane of formula (5) to produce a compound of formula (6); And
(d) reacting the compound of formula (6) with trimethylamine to produce a compound of formula (I), a process for preparing an alkylphosphocholine derivative of formula (I)
Wherein -OH or OR is substituted at the ortho, meta, or para position of benzene,
_Wherein R is- _C10-30 straight or branched chain alkyl; Or -C _10-30 alkyl comprising 1 to 5 double bonds.